Metal oxide nanoparticles are one of the most significant contributors towards the revolutionary change of nanostructured science and technology. Out of many metal oxides, multifunctional iron oxides have paved the way towards applications such as ferrofluids, colour imaging, recording media and magnetic refrigeration. Thrust areas of applications of iron oxides in biological field include contrast agents in MRI, in hyperthermia treatment and drug delivery. The prerequisite for all these applications are smaller size, superparamagnetism, biodegradability, monodispersed, water dispersible particles which have higher stability at room temperature (±20 degrees) and at physiological pH. The smaller size allows nanoparticles to cross through the cellular membranes and avoid the detection by the reticuloendothelial system as well as allow longer blood residence time and subject to rapid renal elimination.
Uncoated magnetite nanoparticles do not form stable dispersions in water at physiological pH. Apart from high surface energy (which is due to high surface area to volume ratio), magnetic nanoparticles also have dipole-dipole interaction which tends the particles to aggregate compared to other non-magnetic counterparts. Thus the particles have to be stabilized which can be done in two ways: either by steric stabilization or by electrostatic stabilization. Steric stabilization is attained by attaching long chain surfactants on to the surface of nanoparticles to prevent the particles from approaching closer, thereby overwhelming the attractive components which tend the particles to aggregate. Electrostatic stabilization is achieved by introducing surface charge onto the nanoparticles, which results in electrostatic repulsion of nanoparticles, hence leading to stabilization of the dispersion.
Number of synthetic strategies are available for the synthesis of particles in organic media at elevated temperatures which leads to hydrophobic fairly monodispersed nanoparticles. Palma et al in Chem Mater 2007, 19, 1821-1831 reported synthesis where hydrophobic ligands are exchanged with hydrophilic to make these particles water dispersible, but the synthesis steps include high temperature as well as harmful organic solvents. Another problem with high temperature synthesis is to keep the bio-molecules at the surface of the particles biologically active at the synthesis temperature or on cooling at room temperatures. Other methods include microemulsion, hydrothermal or sonochemical, which are also not effective in producing the particles with requisite properties.
In biomedical applications, another prerequisite of the nanoparticles is large surface area to volume ratio that allows for the increased loading of therapeutics thereby making them useful in drug delivery.
Curcumin (CUR) a yellow polyphenol compound found in the rhizomes of the plant curcuma longa is known for its excellent anti-oxidant, anti-cancer, anti-inflammatory, and anti-microbial activities, which makes it a promising candidate for coating on iron oxide nanoparticles for biomedical applications. The coating of curcumin on iron oxide nanoparticles with linkers like oleic acid, chitosan and silica has been reported.
Tran et at in Colloids Surf. A: Physicochem. Eng. Aspects, 2010, 371, 104-112 has reported the synthesis of Fe3O4 nanoparticles-curcumin conjugate where curcumin is attached to nanoparticles by using linkers like chitosan and oleic acid. In the above mentioned work, curcumin is indirectly attached onto the magnetite nanoparticles via a linker. Also the author mentions that curcumin is only being adsorbed onto the chitosan or oleic acid coated magnetite nanoparticles. The linker mentioned could not improve the water dispersibility of the prepared fluid.
An article titled “Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications” by Murali M Yallapu, Shadi F Othman et. al. in Int J Nanomedicine. 2012; 7: 1761-1779 having doi: 10.2147/IJN.S29290 disclose formulation composed of an iron oxide core coated with β-cyclodextrin (CD) and pluronic F68 polymer (polyethylene oxide-co-polypropylene oxide-co-polyethylene oxide) and loading anticancer drug curcumin. The article further discloses preparation of magnetic nanoparticles comprising dissolving cyclodextrin, solution of iron(3+) and iron(2+) ions (molar ratio 2:1) in water, ammonium hydroxide, pluronic polymer F68 stirring, washing drying to obtain magnetic nanoparticles (MNC) and followed by loading of curcumin solution in acetone, facilitating the penetration of curcumin molecules (CUR) into the CD or CD-F68 polymer layers in the formulation. MNP-CUR exhibited individual particle grain size of ˜9 nm and hydrodynamic average aggregative particle size of ˜123 nm.
Article titled “Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers” by Wahajuddin and Sumit Arora et. al in Int J Nanomedicine. 2012; 7: 3445-3471 having doi: 10.2147/IJN.S30320 relates to superparamagnetic iron oxide nanoparticles (SPIONs) which are small synthetic γ-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter as novel drug delivery vehicles. The magnetite nanoparticles are obtained by co-precipitation of iron(3+) and iron(2+) ions (molar ratio 2:1) which are further coated with suitable polymers, liposomes, dendrimers etc. Drug loading is achieved either by conjugating the therapeutic molecules on the surface of SPIONs or by coencapsulating drug molecules along with magnetic particles within the coating material envelope.
Article titled “Biomedical properties and preparation of iron oxide-dextran nanostructures by MAPLE technique” by Carmen S Ciobanu, Simona L Iconaru et. al in Chemistry Central Journal 2012, 6:17 doi:10.1186/1752-153X-6-17 relate to dextran coated iron oxide nanoparticles thin films. The dextran-iron oxide continuous thin films are obtained by MAPLE technique from composite targets containing 10 wt. % dextran as well as 1 and 5 wt. % iron oxide nanoparticles synthesized by co-precipitation method. The particle sized calculated was estimated at around 7.7 nm.
Article titled “Encapsulation and Sustained Release of Curcumin using Superparamagnetic Silica Reservoirs” by Suk Fun Chin, K. Swaminathan Iyer et. al having DOI: 10.1002/chem.200802747 disclose synthesis of Fe3O4 nanoparticles by using spinning-disc processing with Fe2+/Fe3+ in aqueous NH4OH. The as-synthesized Fe3O4 nanoparticles were 8-10 nm in size. The article further discloses encapsulation of Fe3O4 nanoparticles and curcumin in mesoporous silica capsules.
The prior art reports on the synthesis of conjugates of magnetic nanoparticles and curcumin with a linker or binder are observed to neither increase the stability of the resulting magnetic fluid nor do they enhance the property of the magnetic iron oxide core or non-magnetic curcumin shell.